Therapeutic Instrumental Music Training and Motor Imagery in Post-Stroke Upper-Extremity Rehabilitation: A Randomized-Controlled Pilot Study.

OBJECTIVE: To investigate the potential benefits of 3 therapeutic instrumental music performance (TIMP)-based interventions in rehabilitation of the affected upper-extremity (UE) for adults with chronic poststroke hemiparesis. DESIGN: Randomized-controlled pilot study. SETTING: University research facility. PARTICIPANTS: Community-dwelling volunteers (N=30; 16 men, 14 women; age range, 33-76 years; mean age, 55.9 years) began and completed the protocol. All participants had sustained a unilateral stroke more than 6 months before enrollment (mean time poststroke, 66.9 months). INTERVENTION: Two baseline assessments, a minimum of 1 week apart; 9 intervention sessions (3 times/week for 3 weeks), in which rhythmically cued, functional arm movements were mapped onto musical instruments; and 1 post-test following the final intervention. Participants were block-randomized to 1 of 3 conditions: group 1 (45 minutes TIMP), group 2 (30 minutes TIMP, 15 minutes metronome-cued motor imagery [TIMP+cMI]), and group 3 (30 minutes TIMP, 15 minutes motor imagery without cues [TIMP+MI]). Assessors and investigators were blinded to group assignment. MAIN OUTCOME MEASURES: Fugl-Meyer Upper-Extremity (FM-UE) and Wolf Motor Function Test- Functional Ability Scale (WMFT-FAS). Secondary measures were motor activity log (MAL)-amount of use scale and trunk impairment scale. RESULTS: All groups made statistically significant gains on the FM-UE (TIMP, P=.005, r=.63; TIMP+cMI, P=.007, r=.63; TIMP+MI, P=.007, r=.61) and the WMFT-FAS (TIMP, P=.024, r=.53; TIMP+cMI, P=.008, r=.60; TIMP+MI, P=.008, r=.63). Comparing between-group percent change differences, on the FM-UE, TIMP scored significantly higher than TIMP+cMI (P=.032, r=.57), but not TIMP+MI. There were no differences in improvement on WMFT-FAS across conditions. On the MAL, gains were significant for TIMP (P=.030, r=.54) and TIMP+MI (P=.007, r=.63). CONCLUSION: TIMP-based techniques, with and without MI, led to significant improvements in paretic arm control on primary outcomes. Replacing a physical training segment with imagery-based training resulted in similar improvements; however, synchronizing internal and external cues during auditory-cMI may pose additional sensorimotor integration challenges.

Functional Brain Network Changes Following Use of an Allostatic, Closed-Loop, Acoustic Stimulation Neurotechnology for Military-Related Traumatic Stress.

BACKGROUND AND PURPOSE: Post-traumatic stress disorder is associated with connectivity changes in the default mode, central executive, and salience networks, and other brain regions. This study evaluated changes in network connectivity associated with usage of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM® ; Brain State Technologies, Scottsdale, AZ), a closed-loop, allostatic, acoustic stimulation neurotechnology, for military-related traumatic stress. METHODS: Eighteen participants (17 males, mean age 41 years [SD = 7], 15 active duty) enrolled in an IRB approved pilot trial for symptoms of military-related traumatic stress. Participants received 19.5 (1.1) HIRREM sessions over 12 days. Symptoms, physiological and functional measures, and whole brain resting MRI were collected before and after HIRREM. Six whole brain functional networks were evaluated using summary variables and community structure of predefined networks. Pre to postintervention change was analyzed using paired-sample statistical tests. RESULTS: Postintervention, there was an overall increase in connectivity of the default mode network (P = .0094). There were decreases of community structure in both the anterior portion of the default mode (medial prefrontal cortex, P = .0097) and in the sensorimotor (P = .005) network. There were no statistically significant changes at the whole brain level, or in the central executive, salience, or other networks analyzed. Participants demonstrated significant improvements in clinical symptoms, as well as autonomic cardiovascular regulation, which have been reported previously. CONCLUSIONS: Use of closed-loop, allostatic, acoustic stimulation neurotechnology (HIRREM) was associated with connectivity changes in the default mode and sensorimotor networks, in directions that may have explained the subjects' clinical improvements.

Effects of supervised exercise and dietary nitrate in older adults with controlled hypertension and/or heart failure with preserved ejection fraction.

Aerobic exercise training is an effective therapy to improve peak aerobic power (peak VO2) in individuals with hypertension (HTN, AHA/ACC class A) and heart failure patients with preserved ejection fraction (HFpEF). High nitrate containing beetroot juice (BRJ) also improves sub-maximal endurance and decreases blood pressure in both HTN and HFpEF. We hypothesized that combining an aerobic exercise and dietary nitrate intervention would result in additive or even synergistic positive effects on exercise tolerance and blood pressure in HTN or HFpEF. We report results from two pilot studies examining the effects of supervised aerobic exercise combined with dietary nitrate in patients with controlled HTN (n = 26, average age 65 ± 5 years) and in patients with HFpEF (n = 20, average age 69 ± 7 years). All patients underwent an aerobic exercise training regimen; half were randomly assigned to consume a high nitrate-containing beet juice beverage (BRJ containing 6.1 mmol nitrate for the HFpEF study consumed three times a week and 8 mmol nitrate for the HTN study consumed daily) while the other half consumed a beet juice beverage with the nitrate removed (placebo). The main result was that there was no added benefit observed for any outcomes when comparing BRJ to placebo in either HTN or HFpEF patients undergoing exercise training (p ≥ 0.14). There were within-group benefits. In the pilot study in patients with HFpEF, aerobic endurance (primary outcome), defined as the exercise time to volitional exhaustion during submaximal cycling at 75% of maximal power output, improved during exercise training within each group from baseline to end of study, 369 ± 149 s vs 520 ± 257 s (p = 0.04) for the placebo group and 384 ± 129 s vs 483 ± 258 s for the BRJ group (p = 0.15). Resting systolic blood pressure in patients with HFpEF also improved during exercise training in both groups, 136 ± 16 mm Hg vs 122 ± 3 mm Hg for the placebo group (p < 0.05) and 132 ± 12 mm Hg vs 119 ± 9 mm Hg for the BRJ group (p < 0.05). In the HTN pilot study, during a treadmill graded exercise test, peak oxygen consumption (primary outcome) did not change significantly, but time to exhaustion (also a primary outcome) improved in both groups, 504 ± 32 s vs 601 ± 38 s (p < 0.05) for the placebo group and 690 ± 38 s vs 772 ± 95 s for the BRJ group (p < 0.05) which was associated with a reduction in supine resting systolic blood pressure in BRJ group. Arterial compliance also improved during aerobic exercise training in both the HFpEF and the HTN patients for both BRJ and placebo groups. Future work is needed to determine if larger nitrate doses would provide an added benefit to supervised aerobic exercise in HTN and HFpEF patients.

Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain.

BACKGROUND: Exercise has positive neuroplastic effects on the aging brain. It has also been shown that ingestion of beet root juice (BRJ) increases blood flow to the brain and enhances exercise performance. Here, we examined whether there are synergistic effects of BRJ and exercise on neuroplasticity in the aging brain. METHODS: Peak metabolic equivalent (MET) capacity and resting-state magnetic resonance imaging functional brain network organization are reported on 26 older (mean age = 65.4 years) participants randomly assigned to 6 weeks of exercise + BRJ or exercise + placebo. RESULTS: Somatomotor community structure consistency was significantly enhanced in the exercise + BRJ group following the intervention (MBRJ = -2.27, SE = 0.145, MPlacebo = -2.89, SE = 0.156, p = .007). Differences in second-order connections between the somatomotor cortex and insular cortex were also significant; the exercise + BRJ group (M = 3.28, SE = 0.167) had a significantly lower number of connections than exercise + placebo (M = 3.91, SE = 0.18, p = .017) following the intervention. Evaluation of peak MET capacity revealed a trend for the exercise + BRJ group to have higher MET capacity following the intervention. CONCLUSIONS: Older adults who exercised and consumed BRJ demonstrated greater consistency within the motor community and fewer secondary connections with the insular cortex compared with those who exercised without BRJ. The exercise + BRJ group had brain networks that more closely resembled those of younger adults, showing the potential enhanced neuroplasticity conferred by combining exercise and BRJ consumption.

Corrigendum: Coping with brief periods of food restriction: mindfulness matters.

[This corrects the article on p. 13 in vol. 4, PMID: 22685430.].

Aging brain from a network science perspective: something to be positive about?

To better understand age differences in brain function and behavior, the current study applied network science to model functional interactions between brain regions. We observed a shift in network topology whereby for older adults subcortical and cerebellar structures overlapping with the Salience network had more connectivity to the rest of the brain, coupled with fragmentation of large-scale cortical networks such as the Default and Fronto-Parietal networks. Additionally, greater integration of the dorsal medial thalamus and red nucleus in the Salience network was associated with greater satisfaction with life for older adults, which is consistent with theoretical predictions of age-related increases in emotion regulation that are thought to help maintain well-being and life satisfaction in late adulthood. In regard to cognitive abilities, greater ventral medial prefrontal cortex coherence with its topological neighbors in the Default Network was associated with faster processing speed. Results suggest that large-scale organizing properties of the brain differ with normal aging, and this perspective may offer novel insight into understanding age-related differences in cognitive function and well-being.

Coping with brief periods of food restriction: mindfulness matters.

The obesity epidemic had spawned considerable interest in understanding peoples' responses to palatable food cues that are plentiful in obesogenic environments. In this paper we examine how trait mindfulness of older, obese adults may moderate brain networks that arise from exposure to such cues. Nineteen older, obese adults came to our laboratory on two different occasions. Both times they ate a controlled breakfast meal and then were restricted from eating for 2.5 h. After this brief period of food restriction, they had an fMRI scan in which they were exposed to food cues and then underwent a 5 min recovery period to evaluate brain networks at rest. On one day they consumed a BOOST® liquid meal prior to scanning, whereas on the other day they only consumed water (NO BOOST® condition). We found that adults high in trait mindfulness were able to return to their default mode network (DMN), as indicated by greater global efficiency in the precuneus, during the post-exposure rest period. This effect was stronger for the BOOST® than NO BOOST® treatment condition. Older adults low in trait mindfulness did not exhibit this pattern in the DMN. In fact, the brain networks of those low on the MAAS suggests that they continued to be pre-occupied with the elaboration of food cues even after cue exposure had ended. Further work is needed to examine whether mindfulness-based therapies alter brain networks to food cues and whether these changes are related to eating behavior.

Holistic approach to treatment of intractable central neuropathic itch.

Central neuropathic itch can be a lifelong debilitating condition and treatment challenge. We report a patient with a traumatic brain injury with severe intractable pruritus who failed extensive pharmacologic and nonpharmacologic treatment but responded to a holistic approach using healing touch. We discuss the complexity of this type of neuropathic itch and present a holistic approach as an adjunct to therapy in reducing itch intensity. This case presentation along with the literature discussed suggests a therapeutic strategy for the management of complicated central neuropathic itch.

Acute effect of a high nitrate diet on brain perfusion in older adults.

AIMS: Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. METHODS AND RESULTS: In this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. CONCLUSION: These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

Aging and the interaction of sensory cortical function and structure.

Even the healthiest older adults experience changes in cognitive and sensory function. Studies show that older adults have reduced neural responses to sensory information. However, it is well known that sensory systems do not act in isolation but function cooperatively to either enhance or suppress neural responses to individual environmental stimuli. Very little research has been dedicated to understanding how aging affects the interactions between sensory systems, especially cross-modal deactivations or the ability of one sensory system (e.g., audition) to suppress the neural responses in another sensory system cortex (e.g., vision). Such cross-modal interactions have been implicated in attentional shifts between sensory modalities and could account for increased distractibility in older adults. To assess age-related changes in cross-modal deactivations, functional MRI studies were performed in 61 adults between 18 and 80 years old during simple auditory and visual discrimination tasks. Results within visual cortex confirmed previous findings of decreased responses to visual stimuli for older adults. Age-related changes in the visual cortical response to auditory stimuli were, however, much more complex and suggested an alteration with age in the functional interactions between the senses. Ventral visual cortical regions exhibited cross-modal deactivations in younger but not older adults, whereas more dorsal aspects of visual cortex were suppressed in older but not younger adults. These differences in deactivation also remained after adjusting for age-related reductions in brain volume of sensory cortex. Thus, functional differences in cortical activity between older and younger adults cannot solely be accounted for by differences in gray matter volume.

Altered temporal profile of visual-auditory multisensory interactions in dyslexia.

Recent studies have demonstrated that dyslexia is associated with deficits in the temporal encoding of sensory information. While most previous studies have focused on information processing within a single sensory modality, it is clear that the deficits seen in dyslexia span multiple sensory systems. Surprisingly, although the development of linguistic proficiency involves the rapid and accurate integration of auditory and visual cues, the capacity of dyslexic individuals to integrate information between the different senses has not been systematically examined. To test this, we studied the effects of task-irrelevant auditory information on the performance of a visual temporal-order-judgment (TOJ) task. Dyslexic subjects' performance differed significantly from that of control subjects, specifically in that they integrated the auditory and visual information over longer temporal intervals. Such a result suggests an extended temporal "window" for binding visual and auditory cues in dyslexic individuals. The potential deleterious effects of this finding for rapid multisensory processes such as reading are discussed.

Aspects of multisensory perception: the integration of visual and auditory information in musical experiences.

One of the requirements for being a successful musical conductor is to be able to locate sounds instantaneously in time and space. Because this requires the integration of auditory and visual information, the purpose of this study was to examine multisensory processing in conductors and a matched set of control subjects. Subjects participated in a series of behavioral tasks, including pitch discrimination, temporal-order judgment (TOJ), and target localization. Additionally, fMRI scans were done on a subset of subjects who performed a multisensory TOJ task. Analyses of behavioral data indicate that, in the auditory realm, conductors were more accurate in both pitch discrimination and TOJs as well as in locating targets in space. Furthermore, these same subjects also demonstrated a benefit from the combination of auditory and visual information that was not observed in control subjects when locating visual targets. Finally, neural substrates in BA 37, 39/40 were identified as potential areas underlying the conductors' superior multisensory TOJs. Data collection and analyses are ongoing and will lead to an improved understanding of multisensory integration in a complex, musical behavior.

Separating neural processes using mixed event-related and epoch-based fMRI paradigms.

Mixed event-related and epoch-based paradigms (mixed designs) have recently been introduced as viable experimental designs for fMRI studies. To date, mixed designs have been used only to evaluate transient and state changes that are associated with single event and blocked conditions, respectively. However, no study exists that demonstrates that the regional activity associated with two distinct processes with known activation patterns can be adequately separated. Rapid event-related experimental designs use the principles of linear summation and can identify multiple distinct processes that are not overlapping in time through linear regression. Events and epochs that are also separated in time can be easily distinguished using the same general linear model (GLM) and a multiple regression analysis. However, it may not be so obvious that events that are superimposed in time onto epochs can also theoretically be separated using this technique. We used the principles of linear summation and the GLM to demonstrate that regional activity from a mixed design with visual epochs and auditory events superimposed in time can in fact be separated. In addition, the flexibility of mixed designs is explored using a paradigm that includes events throughout the on and off blocks of the epoch-based paradigm. Mixed designs provide neuroscientists with the power and flexibility to address more complex cognitive hypotheses that were otherwise difficult to study with either epoch-based or event-related designs alone.

Relationship between caffeine-induced changes in resting cerebral perfusion and blood oxygenation level-dependent signal.

BACKGROUND AND PURPOSE: Recent interest has emerged in the use of pharmacologic methods to maximize blood oxygenation level-dependent (BOLD) signal intensity changes in functional MR imaging (fMRI). Adenosine antagonists, such as caffeine and theophylline, have been identified as potential agents for this purpose. The present study was designed to determine whether caffeine-induced decreases in cerebral perfusion result in enhanced BOLD responses to visual and auditory stimuli. METHODS: MR imaging was used to measure resting cerebral perfusion and stimulus-induced BOLD signal intensity changes in 19 patients. We evaluated the relationship between resting cerebral perfusion and the magnitude of BOLD signal intensity induced by visual and auditory stimulation under caffeine and placebo conditions. RESULTS: The data showed that changes in resting cerebral perfusion produced by caffeine are not a consistent predictor of BOLD signal intensity magnitude. Although all cerebral perfusion was reduced in all study participants in response to caffeine, only 47% of the participants experienced BOLD signal intensity increase. This finding was independent of the participants' usual caffeine consumption. CONCLUSION: The data presented herein show that the relationship between resting cerebral perfusion and the magnitude of BOLD signal intensity is complex. It is not possible to consistently enhance BOLD signal intensity magnitude by decreasing resting perfusion with caffeine. Future studies aimed at evaluating the relationship between perfusion and BOLD signal intensity changes should seek a means to selectively modulate known components of the neural and vascular responses independently.

Cross-modal sensory processing in the anterior cingulate and medial prefrontal cortices.

One of the principal functions of the nervous system is to synthesize information from multiple sensory channels into a coherent behavioral and perceptual gestalt. A critical feature of this multisensory synthesis is the sorting and coupling of information derived from the same event. One of the singular features of stimuli conveying such information is their contextual or semantic congruence. Illustrating this fact, subjects are typically faster and more accurate when performing tasks that include congruent compared to incongruent cross-modal stimuli. Using functional magnetic resonance imaging, we demonstrate that activity in select brain areas is sensitive to the contextual congruence among cross-modal cues and to task difficulty. The anterior cingulate gyrus and adjacent medial prefrontal cortices showed significantly greater activity when visual and auditory stimuli were contextually congruent (i.e., matching) than when they were nonmatching. Although activity in these regions was also dependent on task difficulty, showing decreased activity with decreasing task difficulty, the activity changes associated with stimulus congruence predominated.

Dietary caffeine consumption modulates fMRI measures.

Caffeine is the most widely used stimulant in the world. The stimulant effects of caffeine are mediated through its antagonistic properties on neuronal adenosine receptors. In addition, caffeine blocks neurovascular adenosine receptors and decreases cerebral perfusion. Although the effects of caffeine on blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging measures are extremely important, there are few studies addressing this issue in the literature. Because chronic caffeine use causes an upregulation of adenosine receptors, the differential effects of caffeine in low and high users is of particular interest. The present study was designed to test the hypothesis that caffeine has differential effects on the BOLD signal in high and low caffeine users. We demonstrated that the BOLD signal change in visual cortex was significantly greater in high users than in low users in the presence of caffeine. In addition, the magnitude of the BOLD signal was significantly correlated with caffeine consumption. We propose that the outcome observed here was due to an upregulation of adenosine receptors in high users, resulting in differential contributions of the neural and vascular effects of adenosine in the two study populations.

Deactivation of sensory-specific cortex by cross-modal stimuli.

Visual and auditory cortices traditionally have been considered to be "modality-specific." Thus, their activity has been thought to be unchanged by information in other sensory modalities. However, using functional magnetic resonance imaging (fMRI), the present experiments revealed that ongoing activity in the visual cortex could be modulated by auditory information and ongoing activity in the auditory cortex could be modulated by visual information. In both cases, this cross-modal modulation of activity took the form of deactivation. Yet, the deactivation response was not evident in either cortical area during the paired presentation of visual and auditory stimuli. These data suggest that cross-modal inhibitory processes operate within traditional modality-specific cortices and that these processes can be switched on or off in different circumstances.